Polyphenols from hawthorn peels and fleshes differently mitigate dyslipidemia, inflammation and oxidative stress in association with modulation of liver injury in high fructose diet-fed mice

• Chronic high fructose diet-induced liver injury was related to dyslipidemia, oxidative stress and inflammation in mice.
• The different classes and contents of polyphenols were found in hawthorn peels and fleshes.
• Polyphenols from hawthorn peels and fleshes differently mitigate liver injury induced by high fructose diet.
• Hepatoprotective effects of polyphenols were detected by biochemical tests, western blot assay and histological observation.

Hawthorn ingestion is linked to health benefits due to the various polyphenols. The present study investigated the differential effects of polyphenols-enriched extracts from hawthorn fruit peels (HPP) and fleshes (HFP) against liver injury induced by high-fructose diet in mice. It was found that the main species of polyphenols in hawthorn was chlorogenic acid, epicatechin, rutin and hyperoside, and their contents in HPP were all higher than those in HFP. Administration of HPP was better than HFP to alleviate liver injury and hepatocyte apoptosis, reflected by the reduction of ALT, AST and ALP activities, as well as the ratio of Bax/Bcl-2 in mice. Meanwhile, HPP was also more effective than HFP to mitigate liver inflammation and oxidative stress by inhibiting inflammatory cytokine (TNF-α, IL-1 and IL-6) release, and elevating antioxidant enzyme activities and PPARα expression, while reducing Nrf-2 and ARE expression in mice. Interestingly, HPP-treated mice also showed the lower levels of TC, TG, LDL-C, VLDL-C and Apo-B, and the higher levels of HDL-C and Apo-A1 than HFP-treated mice via reducing FAS express. These results together with the histopathology of the liver with H&E and oil red O staining suggest that hawthorn fruit, especially its peel, is an excellent source of natural polyphenolic chemopreventive agents in the treatment of liver disorders.